Ribonucleic acid (RNA) modifications, once viewed as static structural features, are now recognized as dynamic regulators of the 'epitranscriptome' that shape RNA fate. In cancer, dysregulation of RNA-modification writers, erasers, and readers reprograms RNA metabolism and translation, promoting tumorigenesis, metastasis, therapy resistance, and immune evasion. Across messenger RNAs, ribosomal RNA (rRNAs), transfer (tRNAs), and diverse non-coding RNAs, aberrant modification patterns drive alternative splicing, generate onco-ribosomes, enforce codon-biased translation, and remodel gene-expression networks in a context-dependent manner. This review summarizes how major RNA modifications-including m6A, m5C, pseudouridine, inosine, and ac4C-and their regulators contribute to cancer biology, together with disease-associated changes in rRNA, tRNA, and regulatory non-coding RNAs. We then discuss emerging diagnostic and prognostic biomarkers, druggable nodes within the epitranscriptomic machinery, and combination strategies that integrate RNA-modification targeting with existing therapies and immunotherapy. Finally, we outline key technologies for mapping RNA modifications, comparing mass spectrometry and NGS-based chemical or antibody-enrichment approaches with the expanding capabilities of nanopore direct RNA sequencing. Recent advances in nanopore direct RNA sequencing technologies, leveraging new chemistry (e.g. RNA004) and deep-learning basecallers (e.g. Dorado), increasingly enable single-molecule, multi-modification profiling, accelerating discovery despite inherent technical challenges. Collectively, biological, clinical, and technological progress is transforming the epitranscriptome into a tractable dimension of cancer biology and a promising source of future biomarkers and RNA-targeted precision therapies.
